Polymorphs and amorphous forms of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1h-pyrazole-3-carbonitrile

ABSTRACT

The present invention relates to novel crystalline polymorphs, solvate pseudomorphs and amorphous form of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile (fipronil). The present invention also provides methods for preparing the novel polymorphs, pseudomorphs and amorphous form, as well as insecticidal or pesticidal compositions comprising same, and methods of use thereof as pesticidal agents.

FIELD OF THE INVENTION

The present invention relates to novel crystalline and amorphous formsof5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile (fipronil), to processes for theirpreparation, compositions comprising the new forms, and their use aspesticidal agents.

BACKGROUND OF THE INVENTION

It is known from inter alia, EP-A-0 295 117 and U.S. Pat. No. 5,232,940,that certain N-phenylpyrazole compounds are useful for the control ofarthropod, plant nematode, helminth and protozoan pests. These compoundsinclude N-phenylpyrazoles having an optionally substituted amino groupattached to the 5-position. Such substituted amino groups include aminosubstituted by one or two groups selected from alkyl and alkanoyl.Compounds of interest include those having a cyano group attached to the3-position and a group RS(O)_(n) attached to the 4-position, R beingselected from alkyl and haloalkyl and n being 0, 1 or 2.

Among the compounds in the above-mentioned publications is listed5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulfinylpyrazole, which is depicted as the following formula:

This compound is currently used commercially to control pests in, forexample, agriculture, public health and animal health, and is known asfipronil. Fipronil is a broad spectrum insecticide, toxic by contact andingestion. It is used to control multiple species of thrips on a broadrange of crops by foliar, soil or seed treatment, control of cornrootworm, wireworms and termites by soil treatment in maize and controlof boll weevil and plant bugs on cotton, diamond-back moth on crucifers,Colorado potato beetle on potatoes by foliar application. It is alsowidely used in household pest control including roach and ant controland as a termiticide, as well as for treatment of household pets orother animals.

There is an urgent and unmet need in the art for efficient methods forthe preparation and purification of fipronil, which are simple and canbe used on a large scale for industrial manufacture, and which producehighly pure product that can be safely utilized.

SUMMARY OF THE INVENTION

The present invention relates to novel crystalline polymorphs, solvatepseudomorphs and an amorphous fowl of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile(fipronil). The present invention also provides methods for preparingthe novel polymorphs, pseudomorphs and amorphous form, as well aspesticidal or insecticidal compositions comprising same, and methods ofuse as pesticidal and insecticidal agents.

In one embodiment, the present invention provides a novel crystallinepolymorphic form of fipronil, designated “Form I”. Form I exhibits anX-ray powder diffraction pattern substantially as shown in FIG. 1,having characteristic peaks (expressed in degrees 2θ (+/−0.2° θ) at oneor more of the following positions: 10.3, 11.05, 13.04, 15.93, 16.27,18.48, 19.65, 20.34, 22.05, and 31.55. Form I also exhibits an infrared(IR) spectrum at the 3000 cm⁻¹ range substantially as shown in FIG. 2,having characteristic peaks at about 3332 and 3456. Form I also exhibitsa Differential Scanning calorimetry (DSC) thermogram substantially asshown in FIG. 3, which is characterized by a predominant endotherm peakat about 202.5° C. as measured by Differential Scanning calorimeter at ascan rate of 2° C. and/or 10° C. per minute.

In another embodiment, the present invention provides a novelcrystalline polymorphic form of fipronil designated “Form II”. Form IIexhibits an X-ray powder diffraction pattern substantially as shown inFIG. 4, having characteristic peaks (expressed in degrees 2θ (+/−0.2° θ)at one or more of the following positions: 11.7, 14.4, 15.7, 16.75,17.2, 18.2, 19, 20.7, 22.95, 23.55, and 24.0. Form II also exhibits IRspectrum at the 3000 cm⁻¹ range substantially as shown in FIG. 5, havingcharacteristic peaks at about 3344 and 3436.5 cm⁻¹. Form II alsoexhibits a DSC thermogram substantially as shown in FIG. 6, which ischaracterized by a predominant endotherm at about 195° C., as measuredby Differential Scanning Calorimeter at a scan rate of 2° C. and/or 10°C. per minute.

In another embodiment, the present invention provides a novelcrystalline polymorphic form of fipronil, designated “Form III”. FormIII exhibits an X-ray powder diffraction pattern substantially as shownin FIG. 7, having characteristic peaks (expressed in degrees 2θ (+/−0.2°θ) at one or more of the following positions: 15.6, 16.7, 17.1, 27.2,and 31.9. The DSC of fipronil toluene hemi solvate pseudomorph (FS-T) ata scan rate of 10° C. per minute (FIG. 8) shows an endothermictransformation of FS-T to Form III at ˜110° C. and the exothermictransformation of form III to form I at 150° C.

In another embodiment, the present invention provides a novel toluenehemi solvate pseudomorph of fipronil, designated “FS-T”. The FS-Tpseudomorph exhibits an X-ray powder diffraction pattern substantiallyas shown in FIG. 10, having characteristic peaks (expressed in degrees2θ (+/−0.2° θ) at one or more of the following positions: 7.2, 9.3,12.5, 15.1, 18.65, 19.15, 20.85, 25.95, 28.1, 30.05, and 33.40.Pseudomorph FS-T also exhibits an IR spectrum at the 3000 cm⁻¹ rangesubstantially as shown in FIG. 11, having characteristic peaks at about694.6 and 733.2 cm⁻¹ (toluene solvent); and 3328.4 and 3409.5 cm⁻¹ (NH₂asymmetric and symmetric stretches). Upon stepwise heating to 150° C.and cooling to 60° C., fipronil FS-T converts to Form I, as shown inFIG. 9.

In another embodiment, the present invention provides a novel methylisobutyl ketone (MIBK) hemi solvate pseudomorph of fipronil, designated“FS-M”. The FS-M pseudomorph exhibits an X-ray powder diffractionpattern substantially as shown in FIG. 12, having characteristic peaks(expressed in degrees 2θ (+1-0.2° θ) at one or more of the followingpositions: 6.6, 8.15, 11.85, 19.95, 20.45, 23.10, 26.6, 28.8, and 31.30.Pseudomorph FS-T also exhibits an IR spectrum at the 3000 cm⁻¹ rangesubstantially as shown in FIG. 13, having characteristic peaks at about1710 cm⁻¹ (MIBK ketone); and 3409.5 and 3328 cm⁻¹ (NH₂ asymmetric andsymmetric stretches). Pseudomorph FS-M also exhibits DSC thermogramembedded with TGA (Thermal Gravimetric Analysis) thermogramsubstantially as shown in FIG. 14.

In another embodiment, the present invention provides a novel amorphousfipronil, which exhibits an X-ray powder diffraction patternsubstantially as shown in FIG. 15.

In another embodiment, the present invention provides a mixture ofpolymorphic Form I and Form II of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile(fipronil). Preferably, the mixture comprises from about 10% to about90% by weight of fipronil Form I, and from about 90% to about 10% byweight fipronil Form II.

In another aspect, the present invention provides processes forpreparing the novel polymorphs of fipronil Form I, Form II, Form III,the novel pseudomorphs FS-T and FS-M, and amorphous fipronil.

In one embodiment, Form I fipronil can be prepared by heating a fipronilpseudomorph FS-T to a temperature greater than about 100° C., preferablytemperature of about 150° C., cooling, and isolating the product.Preferably, the process further comprises grinding the pseudomorph FS-T,before, after or during the heating step. An intermediate in theconversion of pseudomorph FS-T to Form I is a novel polymorphic fipronilForm III. As a result of heating FS-T, solvent liberation occursresulting in the formation of Form III, which then undergoes exothermictransition to Form I.

In one embodiment, Form II fipronil can be prepared by crystallizingfipronil from a solvent selected from the group consisting of isopropylalcohol, hexane, ethyl acetate, 1-propanol, butanol, and MIBK, or anymixture of these solvents; and isolating the resulting crystals. In acurrently preferred embodiment, the process includes preparing asolution of the compound in one or more of the aforementioned solvents,preferably by applying heat until dissolution is complete, cooling thesolution until crystals appear (typically 0° C. to room temperature),and isolating the crystals. In one embodiment, the crystallizationsolvent is isopropyl alcohol. In another embodiment, the crystallizationsolvent is a mixture of ethyl acetate and n-hexane. In yet anotherembodiment, the crystallization solvent is a mixture of n-hexane andMIBK. When a solvent mixture is used, fipronil can be dissolved in onesolvent followed by the addition of the other, in any order, or fipronilcan be simultaneously dissolved in the solvent mixture.

In one embodiment, pseudomorph FS-T fipronil can be prepared bycrystallizing fipronil from toluene. In a currently preferredembodiment, the process includes preparing a solution of the compound istoluene, preferably by applying heat until dissolution is complete,cooling the solution until crystals appear (typically 0° C. to roomtemperature), and isolating the crystals.

In one embodiment, pseudomorph FS-M fipronil can be prepared bycrystallizing fipronil from MIBK and n-hexane. Generally, fipronil isdissolved in MIBK and n-hexane (either simultaneously or sequentially),preferably with heat, and the flask is left to stand in the air so thatthe solvent slowly evaporates. Gradually, crystals begin to appear,which are then isolated.

In one embodiment, amorphous fipronil is prepared by heating fipronil toa temperature greater than its melting point (preferably to atemperature greater than about 202.5° C., more preferably to atemperature of about 215° C.), and cooling.

In another aspect, the present invention provides pesticidalcompositions comprising the novel crystalline polymorphs, solvatepseudomorphs and/or the novel amorphous fipronil, which are useful forcontrolling pests. In one embodiment, the compositions comprise apesticidally effective amount of crystalline polymorph Form I fipronil;and an acceptable adjuvant. In another embodiment, the compositioncomprises a pesticidally effective amount of crystalline polymorph FormII of fipronil; and an acceptable adjuvant. In another embodiment, thecomposition comprises a pesticidally effective amount of crystallinepolymorph Form III of fipronil; and an acceptable adjuvant. In yetanother embodiment, the composition comprises a pesticidally effectiveamount of pseudomorph FS-T of fipronil; and an acceptable adjuvant. Inyet another embodiment, the composition comprises a pesticidallyeffective amount of pseudomorph FS-M of fipronil; and an acceptableadjuvant. In yet another embodiment, the composition comprises apesticidally effective amount of an amorphous fipronil; and anacceptable adjuvant. The compositions of the present invention arepreferably intended for use in veterinary medicine, and can beadministered by any method known in the art.

The present invention also relates to methods for controlling pests at alocus, comprising applying to the locus a pesticidally effective amountof a composition of the present invention. In some embodiments the locusis an agricultural locus, including but not limited to agriculturalcrops and fields. In some embodiments the locus is a structure,including but not limited to residential premises, commercial premisesor farmyard structures. In some embodiments the locus is an animal,including wild animals treated to prevent insect borne diseases, as wellas a domestic animal or a household pet including but not limited to adog or a cat. In one preferred embodiment, the composition isadministered topically or by spraying. In some embodiments thecomposition is administered in the form of gels, granules or as bait forpests.

Further embodiments and the full scope of applicability of the presentinvention will become apparent from the detailed description givenhereinafter. However, it should be understood that the detaileddescription and specific examples, while indicating preferredembodiments of the invention, are given by way of illustration only,since various changes and modifications within the spirit and scope ofthe invention will become apparent to those skilled in the art from thisdetailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an X-ray powder diffraction spectrum of fipronil Form I.

FIG. 2: is a FT Infrared spectrum of fipronil Form I (at the 3,000 cm⁻¹range).

FIG. 3: is a Differential Scanning calorimetry (DSC) thermogram offipronil Form I.

FIG. 4 is an X-ray powder diffraction spectrum of fipronil Form II.

FIG. 5: is a FT Infrared spectrum of fipronil Form II (at the 3,000 cm⁻¹range).

FIG. 6: is a Differential Scanning calorimetry (DSC) thermogram offipronil Form II.

FIG. 7: is an X-ray powder diffraction spectrum of a fipronil Form III.

FIG. 8: is a Differential Scanning calorimetry (DSC) thermogram offipronil pseudomorph toluene hemi-solvate (FS-T) and the phasetransition to Form III and to Form I.

FIG. 9: is a Differential Scanning calorimetry (DSC) thermogram offipronil pseudomorph toluene hemi-solvate (FS-T) after heating in stepsto 150° C. and cooling to 60° C.

FIG. 10: is an X-ray powder diffraction spectrum of a fipronilpseudomorph toluene hemi-solvate (F-ST).

FIG. 11: is a FT Infrared spectrum of fipronil F-ST (at the 3,000 cm⁻¹range).

FIG. 12: is an X-ray powder diffraction spectrum of a fipronilpseudomorph MIBK hemi-solvate (F-SM).

FIG. 13: is a FT Infrared spectrum of fipronil F-SM (at the 3,000 cm⁻¹range).

FIG. 14: is a Differential Scanning calorimetry (DSC) thermogramembedded with TGA (Thermal Gravimetric Analysis) thermogram of fipronilF-SM.

FIG. 15: is an X-ray powder diffraction spectrum of amorphous fipronil.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is generally directed to novel crystallinepolymorphic forms of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile (fipronil) referred to herein as“polymorph Form I”, “polymorph Form II”, and “polymorph Form III”. Theinvention is further directed to novel solvate pseudomorphs of fipronil,specifically a toluene hemi-solvate designated herein “pseudomorph.FS-T”, and a methyl isobutyl ketone (MIBK) hemi-solvate designatedherein “pseudomorph FS-M”. The invention is further directed to a novelamorphous form of fipronil. The present invention also provides methodsfor preparing the novel polymorphs, pseudomorphs and amorphous form, aswell as insecticidal or pesticidal compositions comprising same, andmethods of use thereof as pesticidal agents.

Solids exist in either amorphous or crystalline forms. In the case ofcrystalline forms, molecules are positioned in 3-dimensional latticesites. When a compound recrystallizes from a solution or slurry, it maycrystallize with different spatial lattice arrangements, a propertyreferred to as “polymorphism,” with the different crystal formsindividually being referred to as a “polymorph”. Different polymorphicforms of a given substance may differ from each other with respect toone or more physical properties, such as solubility and dissociation,true density, crystal shape, compaction behavior, flow properties,and/or solid state stability.

The inventors of the present applications, after extensiveexperimentation, have discovered three crystalline forms of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile(fipronil), designated Form I, Form II and Form III. The inventors havefurther discovered two new solvate pseudomorphs of fipronil, designatedpseudomorph FS-T (a toluene hemi-solvate) and pseudomorph FS-M (an MIBKhemi-solvate). The inventors have further discovered a novel amorphousform of fipronil. These new Forms exhibit different spectralcharacteristics as depicted by their distinct Differential Scanningcalorimetry (DSC) thermograms, Thermal Gravimetric Analysis (TGA)spectra, X-ray diffraction patterns, and infrared (IR) spectra.

Form I

In one embodiment, the present invention provides a novel crystallinepolymorphic form of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile(fipronil), designated “Form I”. This novel and surprising polymorph maybe characterized by, for example, by DSC, X-Ray powder diffractionspectrometry and/or IR spectrometry.

For example, as shown in FIG. 1, Form I exhibits an X-ray powderdiffraction pattern having characteristic peaks (expressed in degrees 2θ(+/−0.2° θ) at one or more of the following positions: 10.3, 11.05,13.04, 15.93, 16.27, 18.48, 19.65, 20.34, 22.05, and 31.55. The X-Raypowder diffraction were collected on Philips powder diffractometer PW1050/70 operated at 40 kV and 30 mA using CuKα radiation (wavelengthequal to 1.54178 Å) and diffracted beam graphite monochromator. Thetypical θ-2θ scan range is 3-35° 2 Theta with a step size of 0.05° and acount time of 0.5 seconds per step.

The samples were grinded using agate mortar and pestle. The obtainedpowder is then pressed into aluminum sample holder with rectangularcavity of 20 mm*15 mm and of 0.5 mm depth.

Furthermore, as shown in FIG. 2 (showing the 3000 cm⁻¹ range only), FormI also exhibits an Infrared (IR) spectrum having characteristic peaks atabout 3332 and 3456 cm⁻¹, as measured by a Fourier transform infrared(FT-IR) spectrophotometer ReactIR® 1000 of Mettler Toledo Autochem (ATRmethod, MCT detector), diamond window, in DuraSamplIR™ sampling device.The diamond sensor has a standard focusing optic of ZnSe. The powderedsamples were compressed in the sampling device and were measured withresolution of 4 cm⁻¹ and 256 scans.

Furthermore, as shown in FIG. 3, Form I also exhibits a DifferentialScanning Calorimetry (DSC) thermogram which is characterized by apredominant endotherm peak at about 202.5° C. by DSC of Mettler Toledowith 821^(e) module. The weighted samples (2-4 mg) were purged withnitrogen flow during the measurements at a scan rate of 2° C. and/or 10°C. per minute. Aluminum standard pierced crucibles of 40 μL were used.The evaluation is performed using STAR^(e) software. As used herein, theterm “about 202.5° C.” means a range of 201° C. to 204° C. In thisregard, it should be understood that the endotherm measured by aparticular differential scanning calorimeter is dependent upon a numberof factors, including the rate of heating (i.e., scan rate), thecalibration standard utilized, instrument calibration, relativehumidity, and upon the chemical purity of the sample being tested. Thus,an endotherm as measured by DSC on the instrument identified above mayvary by as much as 1.5° C.

In another aspect, the present invention provides processes forpreparing the novel fipronil polymorph Form I. In one embodiment, Form Ican be prepared by heating a fipronil pseudomorph FS-T to a temperaturegreater than about 100° C., preferably a temperature of about 150° C.;cooling, and isolating the product. Generally, although not bylimitation, heating to about 150° C. for about 40 minutes is sufficientto produce fipronil Form I.

Form II

In another embodiment, the present invention provides a novelcrystalline polymorphic form of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile(fipronil), designated “Form II”. This novel and surprising polymorphmay be characterized by, for example, by DSC, X-Ray powder diffractionspectrometry and/or IR spectrometry.

For example, as shown in FIG. 4, Form II exhibits an X-ray powderdiffraction pattern having characteristic peaks (expressed in degrees 2θ(+/−0.2° θ) at one or more of the following positions: 11.7, 14.4, 15.7,16.75, 17.2, 18.2, 19, 20.7, 22.95, 23.55, and 24.0. The X-Ray powderdiffraction was measured as described above.

Furthermore, as shown in FIG. 5 (showing the 3000 cm⁻¹ range only), FormII also exhibits an Infrared (IR) spectrum having characteristic peaksat about 3344 and 3436.5 cm⁻¹, as measured by a Fourier transforminfrared (FT-IR) spectrophotometer as described above.

Furthermore, as shown in FIG. 6, Form II also exhibits a DSC thermogram,which is characterized by a predominant endotherm at about 195° C. (FormII to liquid) at a scan rate of 2° C. and/or 10° C. per minute. Thethermogram further shows an endotherm at about 202° C. resulting fromcrystallization to Form I. The thermogram was measured by a DifferentialScanning calorimeter as described above. As used herein, the term “about195° C.” means from about 193.5° C. to about 196.5° C.

In another aspect, the present invention provides processes forpreparing the novel polymorph Form II. In one embodiment, Form IIfipronil can be prepared by crystallizing fipronil from a solventselected from the group consisting of isopropyl alcohol, hexane, ethylacetate, 1-propanol, butanol, and MIBK, or any mixture of the solvents;and isolating the resulting crystals. In a currently preferredembodiment, the process includes preparing a solution of the compound inone or more of the aforementioned solvents, preferably by applying heatuntil dissolution is complete, cooling the solution until crystalsappear. Generally, cooling the solution to room temperature (definedherein as about 20° C. to about 25° C.) is sufficient, however, thesolution can be cooled to lower temperatures, for example 0° C., 5° C.,10° C., 15° C. and the like. The crystals are then isolated by anyconventional method known in the art, for example by filtration,centrifugation, etc.

In one embodiment, the crystallization solvent is isopropyl alcohol. Inanother embodiment, the crystallization solvent is a mixture of ethylacetate and n-hexane. In yet another embodiment, the crystallizationsolvent is a mixture of n-hexane and MIBK. When a solvent mixture isused, fipronil can be dissolved in one solvent followed by the additionof the other, or fipronil can be simultaneously dissolved in the solventmixture.

Also, the reaction can be seeded with Form II seeds in order to inducecrystallization, as known in the art.

The fipronil starting material used for preparing Form II can be anyform of fipronil, including the fipronil described in U.S. Pat. No.5,232,940, amorphous fipronil, fipronil Form I, fipronil Form III,fipronil FS-T, fipronil FS-M, or any other fipronil known in the art.

Form III

In one embodiment, the present invention provides a novel crystallinepolymorphic form of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile(fipronil), designated “Form III”. This novel and surprising polymorphmay be characterized by, for example, by X-Ray powder diffractionspectrometry.

For example, as shown in FIG. 7, Form III exhibits an X-ray powderdiffraction pattern having characteristic peaks (expressed in degrees 2θ(+/−0.2° θ) at one or more of the following positions: 15.6, 16.7, 17.1,27.2, and 31.9. The X-Ray powder diffraction was measured as describedabove.

The DSC of form FS-T at scan rate of 10° C. per minute (FIG. 8) shows anendothermic transformation of FS-T to Form III at ˜110° C. and theexothermic transformation of form III to form I at 150° C.

In another aspect, the present invention provides processes forpreparing the novel fipronil polymorph Form III. In one embodiment, FormIII is an intermediate in the conversion of pseudomorph FS-T to Form I.As a result of heating FS-T, solvent liberation occurs resulting in theformation of Form III, which then undergoes exothermic transition toForm I.

Form FS-T

In another embodiment, the present invention provides a novel toluenehemi solvate pseudomorph of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile(fipronil), designated “FS-T”. This novel and surprising pseudomorph maybe characterized by, for example, by TGA, X-Ray powder diffractionspectrometry and/or IR spectrometry.

For example, as shown in FIG. 10, pseudomorph FS-T exhibits an X-raypowder diffraction pattern having characteristic peaks (expressed indegrees 2θ (+/−0.2° 0) at one or more of the following positions: 7.2,9.3, 12.5, 15.1, 18.65, 19.15, 20.85, 25.95, 28.1, 30.05, and 33.40. TheX-Ray powder diffraction was measured as described above.

Furthermore, as shown in FIG. 11 (showing the 3000 cm⁻¹ range only),pseudomorph FS-T also exhibits an IR spectrum having characteristicpeaks at about 694.6 and 733.2 cm⁻¹ (toluene solvent); and 3328.4 and3409.5 cm⁻¹ (NH₂ asymmetric and symmetric stretches), as measured by aFourier transform infrared (FT-IR) spectrophotometer as described above.

Upon stepwise heating to 150° C. and cooling to 60° C., fipronil FS-Tconverts to Form I, as shown in FIG. 9.

In another aspect, the present invention provides processes forpreparing the novel pseudomorph FS-T. In one embodiment, fipronil FS-Tcan be prepared by crystallizing fipronil from toluene. In a currentlypreferred embodiment, the process includes preparing a solution of thecompound is toluene, preferably by applying heat until dissolution iscomplete, cooling the solution until crystals appear, and isolating thecrystals. Generally, cooling the solution to room temperature (definedherein as about 20° C. to about 25° C.) is sufficient, however, thesolution can be cooled to lower temperatures, for example 0° C., 5° C.,10° C., 15° C. and the like. The crystals are then isolated by anyconventional method known in the art, for example by filtration,centrifugation, etc.

Also, the reaction can be seeded with pseudomorph FS-T seeds in order toinduce crystallization, as known in the art.

The fipronil starting material used for preparing pseudomorph FS-T canbe any form of fipronil, including the fipronil described in U.S. Pat.No. 5,232,940, amorphous fipronil, fipronil Form I, fipronil Form II,fipronil Form III, fipronil FS-M, or any other fipronil known in theart.

Form FS-M

In another embodiment, the present invention provides a novel methylisobutyl ketone (MIBK) hemi solvate pseudomorph of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile(fipronil), designated “FS-M”. This novel and surprising pseudomorph maybe characterized by, for example, by TGA, X-Ray powder diffractionspectrometry and/or IR spectrometry.

For example, as shown in FIG. 12, pseudomorph FS-M exhibits an X-raypowder diffraction pattern having characteristic peaks (expressed indegrees 2θ (+/−0.2° θ) at one or more of the following positions: 6.6,8.15, 11.85, 19.95, 20.45, 23.10, 26.6, 28.8, and 31.30. The X-Raypowder diffraction was measured as described above.

Furthermore, as shown in FIG. 13 (showing the 3000 cm⁻¹ range only),pseudomorph FS-M also exhibits an IR spectrum substantially as shown inFIG. 8, having characteristic peaks at about 1710 cm⁻¹ (MIBK ketone);and 3409.5 and 3328 cm⁻¹ (NH₂ asymmetric and symmetric stretches), asmeasured by a Fourier transform infrared (FT-IR) spectrophotometer asdescribed above.

Furthermore, pseudomorph FS-M also exhibits a DSC thermogram embeddedwith TGA thermogram substantially as shown in FIG. 14.

In another aspect, the present invention provides processes forpreparing the novel pseudomorph FS-M. In one embodiment, pseudomorphFS-M fipronil can be prepared by crystallizing fipronil from MIBK andn-hexane. Generally, fipronil is dissolved in MIBK and n-hexane (eithersimultaneously or sequentially), preferably with heat, and the flask isleft to stand in the air so that the solvent slowly evaporates.Gradually, crystals begin to appear, which are then isolated. Generally,only a part of the solvent evaporates before the crystals begin toappear, for example about 10-90% of the solvent evaporates in the air,leading to the appearance of crystals.

Also, the reaction can be seeded with pseudomorph FS-M seeds in order toinduce crystallization, as known in the art.

The fipronil starting material used for preparing pseudomorph FS-M canbe any form of fipronil, including amorphous fipronil, fipronil Form I,fipronil Form II, fipronil Form III, fipronil FS-T, or any otherfipronil known in the art.

Amorphous Fipronil

In another embodiment, the present invention provides a novel amorphousfipronil. This novel and surprising amorphous form may be characterizedby, for example, X-Ray powder diffraction spectrometry.

For example, as shown in FIG. 15, the amorphous form has an X-ray powderdiffraction pattern showing no significant signals, indicating anamorphous fipronil solid.

In another aspect, the present invention provides processes forpreparing the novel amorphous fipronil. In one embodiment, amorphousfipronil is prepared by heating fipronil to a temperature greater thanits melting point (preferably to a temperature greater than about 202.5°C., more preferably to a temperature of about 215° C.), and cooling.

The fipronil starting material used for preparing amorphous fipronil canbe any form of fipronil, including amorphous fipronil, fipronil Form I,fipronil Form II, fipronil Form III, fipronil FS-T, fipronil FS-M, orany other fipronil known in the art.

Fipronil Form I and Form II Mixtures

In another embodiment, the present invention provides a mixture ofpolymorphic Form I and Form H of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile(fipronil). Preferably, the mixture comprises from about 10% to about90% by weight of fipronil Form I, and from about 90% to about 10% byweight fipronil Form II. In another embodiment, the mixture comprisesfrom about 20% to about 80% by weight of fipronil Form I, and from about80% to about 20% by weight fipronil Form II. In yet another embodiment,the mixture comprises from about 30% to about 70% by weight of fipronilForm I, and from about 70% to about 30% by weight fipronil Form II. Inyet another embodiment, the mixture comprises from about 40% to about60% by weight of fipronil Form I, and from about 60% to about 40% byweight fipronil Form II. In yet another embodiment, the mixturecomprises about 50% of fipronil Form I, and about 50% by weight fipronilForm II.

In one embodiment, the mixture can be prepared by mixing fipronil Form Iand Form II at the appropriate and desired range.

Compositions and Uses

Fipronil is widely known to be effective in controlling pests. Thus, inanother aspect, the present invention provides pesticidal compositionscomprising the novel crystalline polymorphs, the novel solvatepseudomorphs and/or the novel amorphous fipronil, which are useful forcontrolling pests. In one embodiment, the compositions comprise apesticidally effective amount of crystalline polymorph Form I offipronil; and an acceptable adjuvant. In another embodiment, thecomposition comprises a pesticidally effective amount of crystallinepolymorph Form II of fipronil; and an acceptable adjuvant. In anotherembodiment, the composition comprises a pesticidally effective amount ofcrystalline polymorph Form III of fipronil; and an acceptable adjuvant.In yet another embodiment, the composition comprises a pesticidallyeffective amount of pseudomorph FS-T of fipronil; and an acceptableadjuvant. In yet another embodiment, the composition comprises apesticidally effective amount of pseudomorph FS-M of fipronil; and anacceptable adjuvant. In yet another embodiment, the compositioncomprises a pesticidally effective amount of an amorphous fipronil; andan acceptable adjuvant.

The compositions of the invention can be applied to control pests incompositions of any type known to the art suitable for internal orexternal administration to vertebrates or application for the control ofarthropods in any premises or indoor or outdoor area. All suchcompositions may be prepared in any manner known to the art.

The present invention also provides methods of controlling pests at alocus, by administering the compositions of the present invention.

Examples of the pests that may be controlled are generally described inEuropean Patent Application EP-A-0 295 117 and U.S. Pat. No. 5,232,940,which are incorporated by reference herein in their entirety,Illustrative of specific parasites of various host animals which may becontrolled by the present invention include but are note limited toarthropods such as mites (e.g., mesostigmatids, itch, mange, scabies,chiggers), ticks (e.g., soft-bodied and hard-bodied), lice (e.g.,sucking, biting), fleas (e.g., dog flea, cat flea, oriental rat flea,human flea), true bugs (e.g., bed bugs, Triatomid bugs), bloodsuckingadult flies (e.g., horn fly, horse fly, stable fly, black fly, deer fly,louse fly, tsetse fly, mosquitoes), and parasitic fly maggots (e.g., botfly, blow fly, screwworn, cattle grub, fleeceworm); helminths such asnematodes (e.g., threadworm, lungworm, hookworm, whipworm, nodular worm,stomach worm, round worm, pinworm, heartworm), cestodes (e.g.,tapeworms) and trematodes (e.g., liver fluke, blood fluke); protozoasuch as coccidia, trypanosomes, trichomonads, amoebas and plasmodia;acanthocephalans such as thorny-headed worms (e.g., lingulatulida); andpentastomids such as tongue worms. Arthropod pests that are particularlywell controlled by the present invention are fleas and ticks.

It will be understood that by the term “animals” is meant mammals,preferably domestic animals, e.g., pets, or commercial animals, that is,animals intended to produce a commercial product such as leather orwool, e.g., cows, sheep and horses; and mammals in captivity such aszebras, lions or bears. It will be understood that by the term “pets” ismeant, for example, dogs or cats.

The composition of the invention may further comprise a carrier for usein veterinary medicine, animal health, agriculture, or public health.Such compositions as generally described in EP-A-0 295 117, U.S. Pat.No. 5,232,940, and in U.S. Pat. No. 6,346,542, all of which areincorporated by reference herein in their entirety.

Compositions can be formulated, e.g., for oral, transdermal,percutaneous, e.g. pour-on, or topical administration.

Compositions for oral administration comprise the active ingredienttogether with pharmaceutically acceptable carriers or coatings andinclude, for example, tablets, pills, capsules, pastes, gels, drenches,medicated feeds, medicated drinking water, medicated dietarysupplements, slow-release boluses or other slow-release devices intendedto be retained within the gastro-intestinal tract. Any of these mayincorporate active ingredient contained within microcapsules or coatedwith acid-labile or alkali-labile or other pharmaceutically acceptableenteric coatings. Feed premixes and concentrates containing the novelfipronil Forms for use in preparation of medicated diets, drinking wateror other materials for consumption by animals can also be used.

Compositions for parenteral administration include solutions, emulsionsor suspensions in any suitable pharmaceutically acceptable vehicle andsolid or semisolid subcutaneous implants or pellets designed to releaseactive ingredient over a protracted period and may be prepared and madesterile in any appropriate manner known to the art.

Compositions for percutaneous and topical administration include sprays,dusts, baths, dips, showers, jets, greases, shampoos, creams,wax-smears, or pour-on preparations and devices (e.g. ear tags) attachedexternally to animals in such a way as to provide local or systemicarthropod control.

Solid or liquid baits suitable for controlling arthropods comprise oneor more of the novel Fipronil Forms of the invention and a carrier ordiluent which may include a food substance or some other substance toinduce consumption by the arthropod.

Liquid compositions include water miscible concentrates, emulsifiableconcentrates, flowable suspensions, wettable or soluble powderscontaining one or more of the compounds of the invention which may beused to treat substrates or sites infested or liable to infestation byarthropods including premises, outdoor or indoor storage or processingareas, containers or equipment and standing or running water.

Solid homogenous or heterogenous compositions containing one or more ofthe novel fipronil Forms, for example granules, pellets, briquettes orcapsules, may be used to treat standing or running water over a periodof time. A similar effect may be achieved using trickle or intermittentfeeds of water dispersible concentrates.

Compositions in the form of aerosols and aqueous or non-aqueoussolutions or dispersions suitable for spraying, fogging and low- orultra-low volume spraying can also be used.

Suitable solid diluents which may be used in the preparation of thecompositions of the invention include aluminium silicate, kieselguhr,corn husks, tricalcium phosphate, powdered cork, absorbent carbon black,magnesium silicate, a clay such as kaolin, bentonite or attapulgite, andwater soluble polymers and such solid compositions may, if desired,contain one or more compatible wetting, dispersing, emulsifying orcolouring agents which, when solid, may also serve as diluent.

Such solid compositions, which may take the form of dusts, granules orwettable powders, are generally prepared by impregnating the soliddiluents with solutions of the active ingredient in volatile solvents,evaporating the solvents and, if necessary, grinding the products so asto obtain powders and, if desired, granulating or compacting theproducts so as to obtain granules, pellets or briquettes or byencapsulating finely divided active ingredient in natural or syntheticpolymers, e.g. gelatin, synthetic resins and polyamides.

The wetting, dispersing and emulsifying agents which may be present,particularly in wettable powders, may be of the ionic or non-ionictypes, for example sulphoricinoleates, quaternary ammonium derivativesor products based upon condensates of ethylene oxide with nonyl- andoctylphenol, or carboxylic acid esters of anhydrosorbitols which havebeen rendered soluble by etherification of the free hydroxy groups bycondensation with ethylene oxide, or mixtures of these types of agents.Wettable powders can be treated with water immediately before use togive suspensions ready for application.

Liquid compositions for use in the present invention may take the formof solutions, suspensions and emulsions of the fipronil activeingredient optionally encapsulated in natural or synthetic polymers, andmay, if desired, incorporate wetting, dispersing or emulsifying agents.These emulsions, suspensions and solutions may be prepared usingaqueous, organic or aqueous-organic diluents, for example acetophenone,isophorone, toluene, xylene, mineral, animal or vegetable oils, andwater soluble polymers (and mixtures of these diluents), which maycontain wetting, dispersing or emulsifying agents of the ionic ornon-ionic types or mixtures thereof, for example those of the typesdescribed above. When desired, the emulsions containing the fipronilactive ingredient may be used in the form of self-emulsifyingconcentrates containing the active substance dissolved in theemulsifying agents or in solvents containing emulsifying agentscompatible with the active substance, the simple addition of water tosuch concentrates producing compositions ready for use.

Compositions which can be applied to control arthropod, plant nematode,helminth or protozoan pests, can also contain synergists (e.g. piperonylbutoxide or sesamex), stabilizing substances, other insecticides,acaricides, plant nematocides, anthelmintics or anticoccidials,fungicides (agricultural or veterinary as appropriate e.g. benomyl,iprodione), bactericides, arthropod or vertebrate attractants orrepellents or pheromones, reodorants, flavouring agents, dyes andauxiliary therapeutic agents, e.g. trace elements. These can be designedto improve potency, persistence, safety, uptake where desired, spectrumof pests controlled or to enable the composition to perform other usefulfunctions in the same animal or area treated.

Examples of other pesticidally-active compounds which can be includedin, or used in conjunction with, the compositions of the presentinvention are: acephate, chlorpyrifos, demeton-S-methyl, disulfoton,ethoprofos, fenitrothion, malathion, monocrotophos, parathion,phosalone, pirimiphos-methyl, triazophos, cyfluthrin, cypermethrin,deltamethrin, fenpropathrin, fenvalerate, permethrin, aldicarb,carbosulfan, methomyl, oxamyl, pirimicarb, bendiocarb, teflubenzuron,dicofol, endosulfan, lindane, benzoximate, cartap, cyhexatin,tetradifon, avermectins, ivermectin, milbemycins, thiophanate,trichlorfon, dichlorvos, diaveridine and dimetridazole.

The compositions for application to control pests usually contain from0.00001% to 95%, more particularly from 0.0005% to 50%, by weight of theactive ingredient, alone or together with other substances toxic toarthropods and plant nematodes. The actual compositions employed andtheir rate of application will be selected to achieve the desiredeffect(s) by the farmer, livestock producer, medical or veterinarypractitioner, pest control operator or other person skilled in the art.For example, solid and liquid compositions for application topically toanimals, timber, stored products or household goods usually contain from0.00005% to 90%, more particularly from 0.001% to 10%, by weight of oneor more of the active ingredient. For administration to animals orallyor parenterally, including percutaneously solid and liquid compositionsnormally contain from 0.1% to 90% by weight of one or more of the activeingredient. Medicated feedstuffs normally contain from 0.001% to 3% ofone or more of the active ingredient. Concentrates and supplements formixing with feedstuffs normally contain from 5% to 90%, and preferablyfrom 5% to 50%, by weight of one or more of the active ingredient.Mineral salt licks normally contain from 0.1% to 10% by weight of one ormore of the active ingredient. Dusts and liquid compositions forapplication to livestock, persons, goods, premises or outdoor areas maycontain 0.0001% to 15%, and more especially 0.005% to 2.0%, by weight ofone or more of the active ingredient. Suitable concentrations in treatedwaters are between 0.0001 ppm and 20 ppm, and more especially 0.001 ppmto 5.0 ppm. of one or more of the active ingredient and may also be usedtherapeutically in fish farming with appropriate exposure times. Ediblebaits may contain from 0.01% to 5% and preferably 0.01% to 1.0%, byweight of one or more of the active ingredient.

When administered to vertebrates parenterally, orally or by percutaneousor other means, the dosage of the active ingredient will depend upon thespecies, age and health of the vertebrate and upon the nature and degreeof its actual or potential infestation by arthropod, helminth orprotozoan pest. A single dose of 0.1 to 100 mg, preferably 2.0 to 20.0mg, per kg body weight of the animal or doses of 0.01 to 20.0 mg,preferably 0.1 to 5.0 mg, per kg body weight of the animal per day forsustained medication are generally suitable by oral or parenteraladministration. By use of sustained release formulations or devices, thedaily doses required over a period of months may be combined andadministered to animals on a single occasion.

The following examples are presented in order to more fully illustratecertain embodiments of the invention. They should in no way, however, beconstrued as limiting the broad scope of the invention. One skilled inthe art can readily devise many variations and modifications of theprinciples disclosed herein without departing from the spirit and scopeof the invention.

EXPERIMENTAL DETAILS SECTION Example 1 Preparation of Amorphous Fipronil

5 g. of fipronil (97%) were placed in flask and heated up to 215° C.(above the melting point). The liquid magma was held at that temperaturefor 45 minutes and afterwards was placed in cold iced bath to form theamorphous solid.

X-ray powder diffraction pattern (FIG. 15) shows no significant signals,thus indicating an amorphous Fipronil solid.

Example 2 Preparation of Fipronil Form I and Fipronil Form III

Fipronil Form I is formed by heating and grinding fipronil pseudomorphF-ST up to ˜150° C. for a few minutes. An intermediate in the conversionof pseudomorph FS-T to Form I is a novel polymorphic fipronil Form III.As a result of heating FS-T, solvent liberation occurs resulting in theformation of Form III, which then undergoes exothermic transition toForm I.

Example 3 Preparation of Fipronil Form II

3.1 Crystallization from Isopropanol

2 g. of fipronil was dissolved in 10 g. of isopropyl alcohol at 82° C.The resulting clear solution was slowly cooled to RT and then placed inice/water bath for an hour. White crystalline solid appeared and wasfiltered over filter paper. The resulting solid was dried at 40° C. inthe oven.

mp of the crystals: 195° C. (at 2° C. or 10° C./min).IR bands: 3436.5 and 3344 μm⁻¹

3.2 Crystallization from n-Hexane-Ethyl Acetate

Slurry of 2 g. of fipronil and 90 g. of n-hexane was heated up to 69° C.Ethyl acetate was added dropwise until a clear solution was obtained(total of 71 g.). The solution was then cooled under agitation to roomtemperature. White crystals obtained in the bottom of the flask. Thecrystals were filtered and then dried at 40° C.

mp=196° C. (at 2° C. or 10° C./min).IR bands: 3436.5 and 3344 cm⁻¹

3.3 Crystallization from n-Hexane-Methyl Isobutyl Ketone (MIBK)

A solution of 3 g. fipronil and 10 g. of MIBK was heated to 95° C. Atthat temperature 17.5 g. of n-hexane were added dropwise. The mixturewas cooled at room temperature and then placed in ice/water bath. Whitecrystals were filtered out and then dried at 40° C.

mp=196° C. (at 2° C. or 10° C./min)IR bands: 3436.5 and 3344 cm⁻¹

3.4 Crystallization from 1-Propanol

3 g. of fipronil and 40 g. of 1-propanol were heated to reflux. Thesolution held at reflux for 30 minutes and was cooled to roomtemperature without stirring. Crystals appeared after 2 days andfiltered with vacuum. The crystals were dried at 80° C. overnight. Theresulting crystals were fipronil Form II.

3.5 Crystallization from Butanol

Fipronil was crystallized from butanol as described above in Example3.4, (ratio of 4 g. fipronil to 40 g. of Butanol) resulting in fipronilForm II.

Example 4 Preparation of Fipronil Pseudomorph—Toluene Hemi-Solvate(F-ST)

2 g. of Fipronil and 10 g. of toluene were heated up to 110° C. untilfull dissolution. White crystals appeared within the cooling process toRT. The crystals were filtered and then dried at 40° C. Toluene solvatedetected by TGA (weight loss) and identified via solid state IRmeasurement (peaks at 694.6 and 733.2 cm⁻¹)

IR bands: 3409.5 and 3328.4 cm⁻¹

Example 5 Preparation of Fipronil Pseudomorph—MIBK Hemi-Solvate SM)

2 g. of Fipronil and 10 g. of MIBK (methyl isobutyl ketone) weredissolved at RT. At 100° C. 15.4 g. of n-hexane were added dropwise.White crystalline powder appeared over the flask walls after 12 days atRT while it was left open, and the n-hexane was evaporated from itslowly. The solid was collected from the flask and dried at 40° C. MIBKsolvate detected by TGA (weight loss) and identified via solid state IRmeasurement (peak at 1710 cm⁻¹)

IR bands: 3409.5 and 3328.4 cm⁻¹

While certain embodiments of the invention have been illustrated anddescribed, it will be clear that the invention is not limited to theembodiments described herein. Numerous modifications, changes,variations, substitutions and equivalents will be apparent to thoseskilled in the art without departing from the spirit and scope of thepresent invention as described by the claims, which follow.

1. A form of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoro-methyl)sulfinyl]-1H-pyrazole-3-carbonitrileselected from the group consisting of I. polymorph Form I which exhibitsat least one of the following properties: (a) an X-ray powderdiffraction pattern having characteristic peaks expressed in degrees 2θ(+/−0.20° θ) at about 13.04, 16.27, 18.48, 19.65, 22.05, and 31.55; (b)an X-ray powder diffraction pattern having characteristic peaksexpressed in degrees 2θ (+/−0.20° θ) at about 10.3, 11.05, 13.04, 15.93,16.27, 18.48, 19.65, 20.34, 22.05, and 31.55, substantially as shown inFIG. 1; (c) an infrared (IR) spectrum at the 3000 cm⁻¹, substantially asshown in FIG. 2; or (d) a Differential Scanning calorimeter (DSC)thermogram having a single predominant endotherm at about 202.5° C. asmeasured by a Differential Scanning calorimeter (DSC) at a scan rate of2° C. and/or 10° C. per minute, substantially as shown in FIG. 3; II.polymorph Form II which exhibits at least one of the followingproperties: (a) an X-ray powder diffraction pattern havingcharacteristic peaks expressed in degrees 2θ (+/−0.20° θ) at about 14.4,15.7, 16.75, 17.2, 19, 20.7, 22.95, 23.55, and 32.15; (b) an X-raypowder diffraction pattern having characteristic peaks expressed indegrees 2θ (+/−0.20° θ) at about 11.7, 14.4, 15.7, 16.75, 17.2, 18.2,19, 20.7, 22.95, 23.55, 24.0, and 32.15, substantially as shown in FIG.4; (c) an infrared (IR) spectrum at the 3000 cm⁻¹, having characteristicpeaks at about 3344 and 3436.5 cm⁻¹ substantially as shown in FIG. 5;(d) a Differential Scanning calorimeter (DSC) thermogram having a singlepredominant endotherm at about 195° C. as measured by a DifferentialScanning calorimeter (DSC) at a scan rate of 2° C. and/or 10° C. perminute, substantially as shown in FIG. 6; III. toluene hemi solvate(FS-T) pseudomorph which exhibits at least one of the followingproperties: (a) an X-ray powder diffraction pattern havingcharacteristic peaks expressed in degrees 2θ (+/−0.20° θ) at about 7.2,9.3, 12.5, 17.6, 19.15, 20.85, 28.1, 30.05, and 33.40; (b) an X-raypowder diffraction pattern having characteristic peaks expressed indegrees 2θ (+/−0.20° θ) at about 7.2, 9.3, 12.5, 15.1, 17.6, 18.65,19.15, 20.85, 25.95, 28.1, 30.05, and 33.40, substantially as shown inFIG. 10; (c) an infrared (IR) spectrum at the 3000 cm⁻¹ range, havingcharacteristic peaks at about 694.6, 733.2, 3328.4 and 3409.5 cm⁻¹,substantially as shown in FIG. 11; IV. methyl isobutyl ketone (MIBK)hemi solvate (FS-M) pseudomorph which exhibits at least one of thefollowing properties: (a) an X-ray powder diffraction pattern havingcharacteristic peaks expressed in degrees 2θ (+/−0.20° θ) at about 6.6,8.15, 19.95, 23.10, and 26.6; (b) an X-ray powder diffraction patternhaving characteristic peaks expressed in degrees 2θ (+/−0.20° θ) atabout 6.6, 8.15, 11.85, 19.95, 20.45, 23.10, 26.6, 28.8, and 31.30,substantially as shown in FIG. 12; (c) an infrared (IR) spectrum at the3000 cm⁻¹ range, having characteristic peaks at about 1710, 3409.5 and3328.4 cm⁻¹, substantially as shown in FIG. 13; (d) a DifferentialScanning calorimeter (DSC) thermogram embedded with Thermal GravimetricAnalysis (TGA) thermogram substantially as show in FIG. 14; V. amorphousform which exhibits an X-ray powder diffraction pattern substantially asshown in FIG. 15; and mixtures thereof; and VI. crystalline polymorphicForm III which exhibits at least one of the following properties: (a) anX-ray powder diffraction pattern having characteristic peaks expressedin degrees 2θ (+/−0.20° θ) at about 15.6, 16.7, 27.2, and 31.9; (b) anX-ray powder diffraction pattern substantially a shown in FIG.
 7. 2. Thecrystalline polymorph Form I of claim
 1. 3. The crystalline polymorphForm II of claim
 1. 4. The toluene hemi solvate pseudomorph of claim 1.5. The methyl isobutyl ketone hemi solvate of claim
 1. 6. The amorphouscompound of claim
 1. 7. A mixture of polymorphic Form I and Form II ofclaim
 1. 8. The mixture claim 7 comprising about 10-90% by weight ofpolymorphic Foam I and about 90% to about 10% by weight of polymorphicForm II.
 9. The crystalline polymorph Form III of claim
 1. 10. A processfor the preparation of the crystalline polymorph Form I of claim 2, theprocess comprising the steps of heating a5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-IH-pyrazole-3-carbonitrilepseudomorph FS-T to a temperature greater than about 100° C.; cooling;and isolating the product.
 11. The process according to claim 10,wherein the temperature is about 150° C.
 12. A process for thepreparation of the crystalline polymorph Foam II of claim 3, the processcomprising the steps of crystallizing said compound from a solventselected from the group consisting of isopropyl alcohol, hexane, ethylacetate, 1-propanol, butanol and methyl isobutyl ketone (MIBK), and anymixture of said solvents; and isolating the resulting crystals.
 13. Theprocess according to claim 12, comprising the steps of: (a) preparing asolution of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrilein said solvent or mixture of solvents; (b) cooling the solution so asto form crystals of said compound; and (c) isolating the crystals.
 14. Aprocess for the preparation of the toluene hemi solvate (FS-T)pseudomorph of claim 4, the process comprising the steps ofcrystallizing said compound from toluene; and isolating the resultingcrystals.
 15. The process according to claim 14, comprising the stepsof: (a) preparing a solution of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrilein toluene; (b) cooling the solution so as to form crystals of saidcompound; and (c) isolating the crystals.
 16. The process according toclaim 12, wherein step (a) is conducted with heat.
 17. The processaccording to claim 12, wherein the solution obtained after step (a) iscooled to a temperature of about 0° C. to about room temperature. 18.The process according to claim 12 wherein the crystallization solvent isselected from the group consisting of isopropyl alcohol, 1-propanol,butanol, a mixture of ethyl acetate and n-hexane and a mixture ofn-hexane and MIBK.
 19. A process for the preparation of the methylisobutyl ketone (MIBK) hemi solvate (FS-M) pseudomorph of claim 5, theprocess comprising the steps of preparing a solution of said compound inMIBK and n-hexane; slowly evaporating the solvent; and isolating theresulting crystals.
 20. The process according to claim 19, wherein thesolvent is evaporated by exposing the solution to air.
 21. A process forthe preparation of the amorphous5-amino-1-[2,6-dichloro-4(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrileof claim 6, the process comprising the steps of heating said compound toa temperature greater than its melting point; cooling; and isolating theresulting product.
 22. The process according to claim 21, wherein thetemperature is greater than about 202.5° C.
 23. A pesticidal compositioncomprising: (a) a pesticidally effective amount of a compound accordingto claim 1; and (b) a pesticidally acceptable adjuvant.
 24. Thepesticidal composition according to claim 23 in a form and amounteffective for use in veterinary medicine, agriculture, treating fieldsor crops, household pest control, or roach, ant or termite control. 25.The pesticidal composition according to claim 23, in a form suitable forpercutaneous administration or topical administration.
 26. Thepesticidal composition according to claim 23, in a form suitable for aspray, pest bait, granules, a gel or a solution.
 27. A method forcontrolling pests at a locus, said method comprising applying to saidlocus a pesticidally effective amount of a composition according toclaim 23.